Epstein-Barr Virus-associated Lymphoproliferative Disorder with Encephalitis Following Anti-thymocyte Globulin for Aplastic Anemia Resolved with Rituximab Therapy: A Case Report and Literature Review

Abstract

Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPDs) sometimes occur following Anti-thymocyte globulin (ATG) administration for allogenic stem cell transplantation but are rare in aplastic anemia (AA) patients. A 55-year-old woman with AA following ATG developed refractory fever and was diagnosed with EBV-LPD. She was successfully treated with weekly rituximab monotherapy; however, she developed EBV encephalitis. She was admitted to the intensive care unit and finally recovered from unconsciousness. EBV-LPD should be considered after ATG for AA when symptoms appear. Because EBV-LPD following ATG for AA can rapidly progress, weekly monitoring of EBV-DNA and early intervention may be necessary.

Figure 1.

Photomicrograph of the patient’s bone marrow smear at the time of diagnosis of aplastic anemia. Ninety percent of the normal bone marrow tissue was replaced by adipose tissue with no blasts or mature cells. There were no atypical or malignant cells present. Magnification×100. Hematoxylin and Eosin staining.

Figure 2.

Clinical course of the patient. Forty-five days after ATG initiation, the serum LDH level was elevated to more than 3,000 U/L, and the serum EBV-DNA level increased to 1.1×10⁶ copies/10⁶ cells. Following rituximab therapy, these levels rapidly decreased. Rituximab was administered once a week for 8 weeks.

Figure 3.

Abdominal computed tomography before the initiation of rituximab. Abdominal computed tomography demonstrated hepatosplenomegaly, increased thickness of the gallbladder wall, and multiple enlarged abdominal lymph nodes.

Figure 4.

Southern blot analysis demonstrated monoclonality of the EBV-infected cells. M’ represents the size marker of the DNA; No. 1 is the positive control, No. 2 is the negative control, and No. 3 is the patient’s peripheral blood sample.

Figure 5.

Cranial magnetic resonance imaging (MRI) fluid attenuation inversion recovery imaging. Cranial MRI fluid attenuation inversion recovery imaging revealed high-intensity lesions in the cerebral cortex, in keeping with a diagnosis of viral (EBV) encephalitis.

Figure 6.

Abdominal computed tomography after the eight cycles of rituximab. A CT scan revealed that there was no evidence of hepatosplenomegaly, enlarged gallbladder, or abdominal lymphoadenopathy after treatment with rituximab.